title: Promoter hypermethylation of the EMP3 gene in a series of 229 human gliomas.
abstract: The epithelial membrane protein 3 (EMP3) is a candidate tumor suppressor gene in the critical region 19q13.3 for several solid tumors, including tumors of the nervous systems. The aim of this study was to investigate the EMP3 promoter hypermethylation status in a series of 229 astrocytic and oligodendroglial tumors and in 16 GBM cell lines. The analysis was performed by methylation-specific PCR and capillary electrophoresis. Furthermore, the EMP3 expression at protein level was evaluated by immunohistochemistry and Western blotting analysis. Associations of EMP3 hypermethylation with total 1p/19q codeletion, MGMT promoter hypermethylation, IDH1/IDH2 and TP53 mutations, and EGFR amplification were studied, as well as its prognostic significance. The EMP3 promoter hypermethylation has been found in 39.5% of gliomas. It prevailed in low-grade tumors, especially in gliomas with an oligodendroglial component, and in sGBMs upon pGBMs. In oligodendroglial tumors, it was strongly associated with both IDH1/IDH2 mutations and total 1p/19q codeletion and inversely with EGFR gene amplification. No association was found with MGMT hypermethylation and TP53 mutations. In the whole series, the EMP3 hypermethylation status correlated with 19q13.3 loss and lack of EMP3 expression at protein level. A favorable prognostic significance on overall survival of the EMP3 promoter hypermethylation was found in patients with oligodendroglial tumors.
authors.affiliation: Neuro-Bio-Oncology Center, Policlinico di Monza Foundation (Vercelli)/Consorzio di Neuroscienze, University of Pavia, Via Pietro Micca, 29, 13100 Vercelli, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Mellai
authors.forename: Angela
authors.initials: A
authors.lastname: Piazzi
authors.forename: Valentina
authors.initials: V
authors.lastname: Caldera
authors.forename: Laura
authors.initials: L
authors.lastname: Annovazzi
authors.forename: Oriana
authors.initials: O
authors.lastname: Monzeglio
authors.forename: Rebecca
authors.initials: R
authors.lastname: Senetta
authors.forename: Paola
authors.initials: P
authors.lastname: Cassoni
authors.forename: Davide
authors.initials: D
authors.lastname: Schiffer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002648:Child; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D015254:DNA Modification Methylases / Q000235:genetics; D004252:DNA Mutational Analysis; D045643:DNA Repair Enzymes / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C485157:EMP3 protein, human; D008562:Membrane Glycoproteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; D045643:DNA Repair Enzymes